The long-range goals of this project are: (1)\to elucidate at the molecular level pathogenetic mechanisms involved in the uncontrolled growth of human gliomas; and (2)\to find means of correcting these abnormalities in ways that could be applied clinically. There is evidence that human natural killer (NK) cells can lyse some cultured human glioma and fetal brain cells, but other cells are resistant to such cytolysis. There is also good reason to believe that the glycolipid compositions of these target cells may play a role in determining resistance or sensitivity of cells to NK lysis. In this study, we intend to investigate this important possibility through three sets of experiments. The first set will determine if there is a correlation between the glycolipid composition of cultured human glioma and normal fetal brain cells, and their susceptibility to NK cytolysis. In the second set of experiments, we will exploit the finding that interferon can alter the susceptibilty of some cells to NK attack. The same types of target cells will be preincubated with human fibroblast interferon and then assayed for both their glycolipid compositions and susceptibility to NK lysis. Correlations will be sought between altered susceptibility to NK lysis and alterations of glycolipid compositions. The third set of experiments will determine if susceptibility to NK lysis can be altered by preincubating the target cells with specific glycolipids suspected on the basis of results from the first two sets of experiments to confer susceptibility or resistance to NK cytolysis.